Considerable evidence has been derived from structural investigations of plasma-cytoma proteins and genetic studies of immunoglobulins indicating that two discrete structural genes govern the synthesis of a single immunoglobulin polypeptide chain. In order to gain additional insight as to the genetic mechanism of normal immunoglobulin formation, we propose to analyze the structure of a mutant IgG myeloma protein. This protein was produced in a patient with myeloma and represents the first reported case associated with the synthesis of an IgG molecule containing lambda-type L chains in which both H and L chains contain deletions. Previous studies from our laboratory have established that the lambda chain contains an internal deletion of 81 amino acid residues which is entirely restricted to the variable region. We now plan to define the nature and extent of the deletion of the gamma chain. Since these immunoproteins appear to result from an abnormality of gene expression, localization of the deleted portion of the polypeptide may clarify the mechanism of gene translocation - the fusion of genes responsible for heavy or light chain synthesis, which may be the key signal in immunocyte differentiation. A second objective is to determine the primary structure of the H and L chains of an unusual human IgG myeloma protein which has antibody-like activity to the vitamin riboflavin. In addition, affinity-labeling experiments will also be pursued in attempts to locate the combining site of the antibody. These studies could provide information on the molecular basis of antibody specificity and the nature of antigen-antibody interactions.